text: The modern perspective is that rate-limitingness should be quantitative and that it is distributed through a pathway to varying degrees. This idea was first considered by Higgins in the late 1950s as part of his PhD thesis where he introduced the quantitative measure he called the ‘reflection coefficient.’ This described the relative change of one variable to another for small perturbations. In his Ph.D. thesis, Higgins describes many properties of the reflection coefficients, and in later work, three groups, Savageau, Heinrich and Rapoport and Jim Burns in his thesis (1971) and subsequent publications independently and simultaneously developed this work into what is now called metabolic control analysis or, in the specific form developed by Savageau, biochemical systems theory. These developments extended Higgins’ original ideas significantly, and the formalism is now the primary theoretical approach to describing deterministic, continuous models of biochemical networks.
  The variations in terminology between the different papers on metabolic control analysis were later harmonized by general agreement.